Human pulmonary alveolar macrophages (HAMs) have been shown to possess high elastase-like esterase activity. However, this esterase activity does not correlate with assays using elastic tissue as substrate. HAMs obtained from cigarette smokers do contain true elastolytic activity when tritium labeled elastic is used as substrate. This activity is low compared to pancreatic elastase or leukocyte granule elastase. HAM elastase activity is present in the cytosol fraction of carefully disrupted cells and is not associated with the granule fraction. The absence of other lysosomal enzymes from this cytosol fraction suggests a unique compartmentalization of elastase as an unusual lability of elastase storage granules. When HAMs are maintained in tissue culture for 3-7 days, elastase activity appears in the culture media. The appearance of elastase activity is not associated with a loss of cell viability. Current studies are directed toward isolation and purification of HAM elastase by affinity chromatography and further characterization of the enzyme(s). BIBLIOGRAPHIC REFERENCES: Fromm, G., Harris, J., and Dunn, L.: Characterization of free intra-alveolar cells in desquamative interstitial pneumonia. Clin. Research 25:37A, 1977.